In addition to Hox genes, Pim1, Notch1, and downregulation of INK4A-ARF by Bmi-1 have also been shown to cooperate with E2A-PBX1 in oncogenesis suggesting the importance of secondary hits in the development of E2A-PBX1 driven leukemias (24–26). This evidence concerns the gene CDKN2A and leukemia.